Omeprazole, which has the chemical structural formula: ##STR1## is a known gastric acid secretion inhibiting agent, and is prescribed clinically for the prevention and treatment of gastrointestinal inflammatory diseases in mammals including man, for example gastritis, gastric ulcer and duodenal ulcer. Lansoprazole, which has the chemical structural formula: ##STR2## has similar pharmaceutical activity and medicinal uses.
The reported syntheses of omeprazole basically involve the synthesis of the corresponding thioether compound, of the formula: ##STR3## and its subsequent oxidation to the sulfinyl or sulfoxy compound, omeprazole, by various methods such as reaction with hydrogen peroxide over a vanadium compound catalyst (Canadian Patent 1,263,119 Takeda), reaction with peracids, peresters, ozone, etc. (Canadian patent 1,127,158) . Lansoprazole similarly is produced by oxidation of the thioether compound of formula: ##STR4## There are certain disadvantages associated with these processes, largely derived from the nature of the thioether (or sulfide) compound being oxidized.
One of these disadvantages derives from the physical nature of the thioether itself. Under ordinary conditions of temperature and pressure, it is an oil, not a crystalline solid. Accordingly, it is very difficult to purify, since it cannot be subjected to precipitation and crystallization procedures to remove impurities from it. This leads to complications in the processes for purifying the resultant omeprazole.
Another disadvantage associated with both omeprazole and lansoprazole derives from the discolouration of the final product made by oxidation of the thioethers. A red discolouration of the crude products is commonly experienced, and is very difficult to avoid, using this oxidation process. Omeprazole and lansoprazole are inherently unstable molecules in weakly acidic conditions, tending to rearrange to produce annoying highly coloured decomposition impurities.